Over the past century the development of agents to combat infections, such as viral infections, fungal infections, bacterial infections and the like, has vastly increased the average lifespan throughout the world. However, pathogens are increasingly developing ways to avoid or circumvent existing therapeutics. For example, the widespread use of traditional antibiotics, such as penicillin and related compounds has resulted in the development of bacteria that are resistant to these traditional antibiotics, as exemplified by the rise of methicillin resistant Staphylococcus aureus (MRSA). Similarly, viral pathogens, such as HIV, are able to acquire resistance to antivirals within a few replication cycles.
To combat the ever-changing landscape of pathogens and emerging resistance to the current therapies, the standard course of action for pharmaceutical companies is to develop an ever-increasing array of small molecule therapeutic agents. As an alternative, vaccines have been developed which stimulate the body to fight an infection by eliciting antibody responses to the target pathogen(s).
Antibodies protect against pathogen attack by recognizing and binding to antigens on the pathogen to facilitate the removal or “clearance” of the pathogens by a process called phagocytosis, wherein phagocytic cells (for example neutrophils and macrophages) identify, engulf, and subsequently destroy the pathogens. However, some pathogens, such as certain bacteria, can avoid phagocytosis. Bacteria can produce a “capsule” that inhibits phagocyte adherence. Opsonic antibodies overcome these defenses by binding to the capsule or to other target antigens on the bacterium, in a process called opsonization. This triggers the complement cascade, to produce a set of serum proteins with opsonic and lytic activities. Opsonic antibodies with complement components, such as C3a and C5a, bind the bacteria to make the bacteria extremely attractive to phagocytes and enhance the rate of clearance from the bloodstream. Recently, researchers have exploited opsonic antibodies by purifying opsonic antibodies and administering these antibodies to subjects in order to treat infections. While the use of opsonic antibodies has shown some promises in treating and/or preventing infection by pathogens, the need exists for enhancing the efficacy of these antibodies, for example to reduce the amount of the opsonic antibodies needed to achieve a therapeutically effective result. The methods disclosed herein meet those needs.